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A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice

Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected...

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Autores principales: Alves, Joana, Madureira, Pedro, Baltazar, Maria Teresa, Barros, Leandro, Oliveira, Liliana, Dinis-Oliveira, Ricardo Jorge, Andrade, Elva Bonifácio, Ribeiro, Adília, Vieira, Luís Mira, Trieu-Cuot, Patrick, Duarte, José Alberto, Carvalho, Félix, Ferreira, Paula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682941/
https://www.ncbi.nlm.nih.gov/pubmed/26673420
http://dx.doi.org/10.1371/journal.pone.0144196
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author Alves, Joana
Madureira, Pedro
Baltazar, Maria Teresa
Barros, Leandro
Oliveira, Liliana
Dinis-Oliveira, Ricardo Jorge
Andrade, Elva Bonifácio
Ribeiro, Adília
Vieira, Luís Mira
Trieu-Cuot, Patrick
Duarte, José Alberto
Carvalho, Félix
Ferreira, Paula
author_facet Alves, Joana
Madureira, Pedro
Baltazar, Maria Teresa
Barros, Leandro
Oliveira, Liliana
Dinis-Oliveira, Ricardo Jorge
Andrade, Elva Bonifácio
Ribeiro, Adília
Vieira, Luís Mira
Trieu-Cuot, Patrick
Duarte, José Alberto
Carvalho, Félix
Ferreira, Paula
author_sort Alves, Joana
collection PubMed
description Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice against GBS infections. It is therefore a promising candidate as a global vaccine to prevent GBS-induced neonatal and adult diseases.
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spelling pubmed-46829412015-12-31 A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice Alves, Joana Madureira, Pedro Baltazar, Maria Teresa Barros, Leandro Oliveira, Liliana Dinis-Oliveira, Ricardo Jorge Andrade, Elva Bonifácio Ribeiro, Adília Vieira, Luís Mira Trieu-Cuot, Patrick Duarte, José Alberto Carvalho, Félix Ferreira, Paula PLoS One Research Article Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice against GBS infections. It is therefore a promising candidate as a global vaccine to prevent GBS-induced neonatal and adult diseases. Public Library of Science 2015-12-16 /pmc/articles/PMC4682941/ /pubmed/26673420 http://dx.doi.org/10.1371/journal.pone.0144196 Text en © 2015 Alves et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Alves, Joana
Madureira, Pedro
Baltazar, Maria Teresa
Barros, Leandro
Oliveira, Liliana
Dinis-Oliveira, Ricardo Jorge
Andrade, Elva Bonifácio
Ribeiro, Adília
Vieira, Luís Mira
Trieu-Cuot, Patrick
Duarte, José Alberto
Carvalho, Félix
Ferreira, Paula
A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice
title A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice
title_full A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice
title_fullStr A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice
title_full_unstemmed A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice
title_short A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice
title_sort safe and stable neonatal vaccine targeting gapdh confers protection against group b streptococcus infections in adult susceptible mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682941/
https://www.ncbi.nlm.nih.gov/pubmed/26673420
http://dx.doi.org/10.1371/journal.pone.0144196
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